Coverage Policy Manual - Arkansas Blue Cross and Blue Shield

Coverage Policy Manual
Policy #:	2018014
Category:	Pharmacy
Initiated:	April 2018
Last Review:	July 2023

Lutetium Lu 177 Dotatate (e.g., Lutathera®)

Description:

Lutetium Lu 177 Dotatate is a radiolabeled somatostatin analog indicated for the treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults.

Lutetium Lu 177 dotatate binds to somatostatin receptors with highest affinity for subtype 2 receptors (SSRT2). Upon binding to somatostatin receptor expressing cells, including malignant somatostatin receptor-positive tumors, the compound is internalized. The beta emission from Lu 177 induces cellular damage by formation of free radicals in somatostatin receptor-positive cells and in neighboring cells.

Regulatory Status

Lutathera® was FDA-approved in January 2018 for the treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults (U.S. Food and Drug Administration 2018).

Coding

See CPT/HCPCS Code section below.

Policy/
Coverage:

Effective August 1, 2021, for members of plans that utilize a radiation oncology benefits management program, Prior Approval is required for this service and is managed through the radiation oncology benefits management program.

Effective May 01, 2018, Prior Approval is required for Lutetium Lu 177 Dotate.

The Step Therapy Medication Act is applicable to fully insured (Arkansas Blue Cross, Health Advantage, and Exchange) and specified governmental (ASE/PSE and ASP) health plans. The law is not applicable to FEP or self-insured ERISA groups (including but not limited to Walmart or other Blue Advantage groups). Initial approval for exigent request is 28 days. Otherwise, initial approval for standard review is up to 1 year.

The initial use of this drug requires documentation of direct physician involvement and signature in the ordering and evaluation as documented in the medical records submitted for prior approval.

Effective July 12, 2023

Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria

A single course of up to 4 planned injections of Lutetium Lu 177 dotatate meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for the treatment of locally advanced, unresectable, or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NET), including foregut, midgut, and hindgut neuroendocrine tumors when ALL of the following conditions are met:

Individual is age 18 years or older.
An appropriate imaging study has been performed to document somatostatin receptor overexpression.
Disease has progressed on at least 4 months of somatostatin receptor analog therapy and documented by radiographic imaging. (Strosberg 2017)

4. Tumor is well-differentiated (Ki-67 of <55%) [NCCN 2A]

OFF LABEL

Neuroendocrine Tumors of the Gastrointestinal Tract (Well-Differentiated Grade 1/2), Lung, and Thymus

Preferred management of recurrent, locoregional advanced disease and/or distant metastases of the gastrointestinal tract if somatostatin receptor positive and prior progression on octreotide LAR or lanreotide (NCCN 1 for progressive mid-gut tumors; NCCN 2A for all others):

a. As alternative-front-line therapy for clinically significant tumor burden.

b. As subsequent therapy.

2. Consider as subsequent therapy for management of recurrent and/or locoregional unresectable bronchopulmonary/thymic disease if somatostatin receptor positive and progression on octreotide LAR/lanreotide. (NCCN 2A)

3. Management of recurrent and/or distant metastatic bronchopulmonary/thymic disease if somatostatin receptor positive and progression on octreotide LAR/lanreotide in individuals with clinically significant tumor burden and low grade, evidence of disease progression, intermediate grade, or symptomatic disease. (NCCN 2A):

a. As primary therapy.

b. Consider as subsequent therapy (as alternate primary therapy) if progression on primary therapy.

4. Consider for poorly controlled carcinoid syndrome if somatostatin receptor positive and progression on octreotide LAR or lanreotide for persistent symptoms in combination with (NCCN 1 for progressive mid-gut tumors; NCCN 2A for all others):

a. Either octreotide LAR or lanreotide.

b. Telotristat for persistent diarrhea and either octreotide LAR or lanreotide.

Neuroendocrine Tumors of the Pancreas (Well-Differentiated Grade 1/2)

Preferred for the management of symptomatic, clinically significant tumor burden, or progressive recurrent, locoregional advanced disease and/or distant metastatic disease if somatostatin receptor positive and progression on octreotide LAR or lanreotide. (NCCN 2A)

a. As alternative front-line therapy.

b. As subsequent therapy if disease progression.

Well-Differentiated Grade 3 Neuroendocrine Tumors

Treatment for unresectable locally advanced/metastatic disease with favorable biology that has clinically significant tumor burden or evidence of disease progression if SSTR-positive. (NCCN 2A)

Pheochromocytoma/Paraganglioma

Consider as primary treatment for secreting tumors if somatostatin receptor positive for (NCCN 2A):

a. Locally unresectable disease.

b. Distant metastases.

The use of this drug is covered if a FDA-approved oncologic indication exists (not listed as an indication above) with the member meeting all of the additional requirements of the prescribing information (package insert listed in the “Indications and Usage”) AND/OR a NCCN category 1 or 2A recommendation is recognized in the NCCN Drugs and Biologics Compendium with the member meeting specified criteria (See policy #2000030).

Dosing and Administration

Dosing per FDA Guidelines

The prescribed regimen must be in compliance with FDA-approved dosing, with a dosing regimen of 7.4 GBq (200 mCi) every 8 weeks for a total of 4 doses (limited to one 4-dose regimen per lifetime).

Somatostatin Analogs

Before initiating Lutetium Lu 177 dotatate: Discontinue long-acting somatostatin analogs (e.g., long-acting octreotide) for at least 4 weeks prior to initiating Lutathera®. Administer short-acting octreotide as needed; discontinue at least 24 hours prior to initiating Lutathera®.
During Lutetium Lu 177 dotatate treatment: Administer long-acting octreotide 30 mg intramuscularly between 4 to 24 hours after each Lutetium Lu 177 dotatate dose. Do not administer long-acting octreotide within 4 weeks of each subsequent Lutetium Lu 177 dotatate dose. Short-acting octreotide may be given for symptomatic management during Lutetium Lu 177 dotatate treatment but must be withheld for at least 24 hours before each Lutathera® dose.
Following Lutetium Lu 177 dotatate treatment: Continue long-acting octreotide 30 mg intramuscularly every 4 weeks after completing Lutetium Lu 177 dotatate until disease progression or for up to 18 months following treatment initiation.

Amino Acid Solution

Administer IV amino acid solution in accordance with FDA labeling when infusing Lutetium Lu 177 dotatate.

Lutetium Lu 177 dotatate is available as 370 MBq/mL (10 mCi/mL) in single-dose vial.

Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.

Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria

Lutetium Lu 177 dotatate does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when:

The above criteria are not met and for all other indications.
Given as a repeat course of treatment (Note: A course can include up to 4 planned injections)

For members with contracts without primary coverage criteria, Lutetium Lu 177 dotatate is considered investigational when:

The above criteria are not met and for all other indications.
Given as a repeat course of treatment (Note: A course can include up to 4 planned injections)

Investigational services are specific contract exclusions in most member benefit certificates of coverage.

Effective January 2022 to July 11, 2023

Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria

A single course of up to 4 planned injections of Lutetium Lu 177 dotatate meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for the treatment of locally advanced, unresectable, or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NET) or locally advanced bronchopulmonary and thymic neuroendocrine tumors when ALL of the following conditions are met:

Individual is age 18 years or older
An appropriate imaging study has been performed to document somatostatin receptor overexpression
Disease has progressed on at least 4 months of somatostatin receptor analog therapy and documented by radiographic imaging. (Strosberg 2017)
Tumor is well-differentiated (Ki-67 of <55%) [NCCN 2A]

Off Label

For management as primary therapy or subsequent therapy if progression on first line therapy for distant metastatic bronchopulmonary/thymic disease if somatostatin receptor positive and progression on octreotide/lanreotide in patients with clinically significant tumor burden and low grade (typical carcinoid) histology, evidence of progression, intermediate grade, (atypical carcinoid) histology, or symptomatic. (NCCN 2A)
Preferred management of locoregional advanced disease of the gastrointestinal tract and/or distant metastases for clinically significant tumor burden or somatostatin receptor positive imaging on octreotide/lanreotide. (NCCN 1 progressive mid-gut tumors; NCCN 2A all others)
For poorly controlled carcinoid syndrome if somatostatin receptor positive imaging and progression on octreotide in combination with either octreotide LAR or lanreotide for persistent symptoms or telotristat for persistent diarrhea. (NCCN 1 progressive mid-gut tumors; NCCN 2A all others)
For gastrinoma, glucagonoma, Insulinoma or VIPoma when symptomatic, clinically significant tumor burden, or progress locoregional advanced disease and/or distant metastatic disease if somatostatin receptor positive and progression on octreotide/lanreotide. (NCCN 2A)
For locally unresectable or metastatic pheochromocytoma or paraganglioma. (NCCN 2A)

Dosing and Administration

The prescribed regimen must be in compliance with FDA-approved dosing, with a dosing regimen of 7.4 GBq (200 mCi) every 8 weeks for a total of 4 doses (limited to one 4-dose regimen per lifetime).

Somatostatin Analogs

Before initiating Lutetium Lu 177 dotatate: Discontinue long-acting somatostatin analogs (e.g., long-acting octreotide) for at least 4 weeks prior to initiating Lutathera®. Administer short-acting octreotide as needed; discontinue at least 24 hours prior to initiating Lutathera®.
During Lutetium Lu 177 dotatate treatment: Administer long-acting octreotide 30 mg intramuscularly between 4 to 24 hours after each Lutetium Lu 177 dotatate dose. Do not administer long-acting octreotide within 4 weeks of each subsequent Lutetium Lu 177 dotatate dose. Short-acting octreotide may be given for symptomatic management during Lutetium Lu 177 dotatate treatment, but must be withheld for at least 24 hours before each Lutathera® dose.
Following Lutetium Lu 177 dotatate treatment: Continue long-acting octreotide 30 mg intramuscularly every 4 weeks after completing Lutetium Lu 177 dotatate until disease progression or for up to 18 months following treatment initiation.

Amino Acid Solution

Administer IV amino acid solution in accordance with FDA labeling when infusing Lutetium Lu 177 dotatate.

Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.

Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria

Lutetium Lu 177 dotatate does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness when:

• The above criteria are not met and for all other indications

• Given as a repeat course of treatment (Note: A course can include up to 4 planned injections)

For members with contracts without primary coverage criteria, Lutetium Lu 177 dotatate is considered investigational when:

The above criteria are not met and for all other indications

• Given as a repeat course of treatment (Note: A course can include up to 4 planned injections)

Investigational services are specific contract exclusions in most member benefit certificates of coverage.

Effective November 2021 through December 31, 2021

Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria

A single course of up to 4 planned injections of Lutetium Lu 177 dotatate (Lutathera®) meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for the treatment of locally advanced, unresectable, or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NET) or locally advanced bronchopulmonary and thymic neuroendocrine tumors when ALL of the following conditions are met:

• Individual is age 18 years or older

• An appropriate imaging study has been performed to document somatostatin receptor overexpression

• Disease has progressed on at least 4 months of somatostatin receptor analog therapy and documented by radiographic imaging

• Tumor is well-differentiated (Ki-67 of 20% or less)

Dosing and Administration

The prescribed regimen must be in compliance with FDA-approved dosing, with a dosing regimen of 7.4 GBq (200 mCi) every 8 weeks for a total of 4 doses (limited to one 4-dose regimen per lifetime).

Somatostatin Analogs

Before initiating Lutetium Lu 177 dotatate: Discontinue long-acting somatostatin analogs (e.g., long-acting octreotide) for at least 4 weeks prior to initiating Lutathera®. Administer short-acting octreotide as needed; discontinue at least 24 hours prior to initiating Lutathera®.
During Lutetium Lu 177 dotatate treatment: Administer long-acting octreotide 30 mg intramuscularly between 4 to 24 hours after each Lutathera® dose. Do not administer long-acting octreotide within 4 weeks of each subsequent Lutathera® dose. Short-acting octreotide may be given for symptomatic management during Lutathera® treatment, but must be withheld for at least 24 hours before each Lutathera® dose.
Following Lutetium Lu 177 dotatate treatment: Continue long-acting octreotide 30 mg intramuscularly every 4 weeks after completing Lutathera® until disease progression or for up to 18 months following treatment initiation.

Amino Acid Solution

Administer IV amino acid solution in accordance with FDA labeling when infusing Lutetium Lu 177 dotatate.

Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.

Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria

Lutetium Lu 177 dotatate (Lutathera®) does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness when:

• The above criteria are not met and for all other indications

• Given as a repeat course of treatment (Note: A course can include up to 4 planned injections)

For members with contracts without primary coverage criteria, Lutetium Lu 177 dotatate (Lutathera) is considered investigational.

Investigational services are specific contract exclusions in most member benefit certificates of coverage.

Effective July 2021 to October 31, 2021

Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria

• Individual is age 18 years or older

• An appropriate imaging study has been performed to document somatostatin receptor overexpression

• Disease has progressed on at least 4 months of somatostatin receptor analog therapy and documented by radiographic imaging

• Tumor is well-differentiated (Ki-67 of 20% or less)

NCCN 1, 2A, and 2B recommendations in accordance with Coverage Policy #2000030.

Dosing and Administration

The prescribed regimen must be in compliance with FDA-approved dosing, with a dosing regimen of 7.4 GBq (200 mCi) every 8 weeks for a total of 4 doses (limited to one 4-dose regimen per lifetime).

Somatostatin Analogs

Before initiating Lutetium Lu 177 dotatate: Discontinue long-acting somatostatin analogs (e.g., long-acting octreotide) for at least 4 weeks prior to initiating Lutathera®. Administer short-acting octreotide as needed; discontinue at least 24 hours prior to initiating Lutathera®.
During Lutetium Lu 177 dotatate treatment: Administer long-acting octreotide 30 mg intramuscularly between 4 to 24 hours after each Lutathera® dose. Do not administer long-acting octreotide within 4 weeks of each subsequent Lutathera® dose. Short-acting octreotide may be given for symptomatic management during Lutathera® treatment, but must be withheld for at least 24 hours before each Lutathera® dose.
Following Lutetium Lu 177 dotatate treatment: Continue long-acting octreotide 30 mg intramuscularly every 4 weeks after completing Lutathera® until disease progression or for up to 18 months following treatment initiation.

Amino Acid Solution

Administer IV amino acid solution in accordance with FDA labeling when infusing Lutetium Lu 177 dotatate.

Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.

Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria

Lutetium Lu 177 dotatate (Lutathera®) does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness when:

• The above criteria are not met and for all other indications

• Given as a repeat course of treatment (Note: A course can include up to 4 planned injections)

For members with contracts without primary coverage criteria, Lutetium Lu 177 dotatate (Lutathera) is considered investigational.

Investigational services are specific contract exclusions in most member benefit certificates of coverage.

Effective April 2019 to June 2021

Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria

Lutetium Lu 177 dotatate meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness and is covered for the following indications:

Treatment of well-differentiated somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults when all of the following conditions are met:

Tumors must be metastasized or locally advanced, inoperable, and showed disease progression during treatment with a somatostatin analogue (octreotide or lanreotide) AND
Patients must have a Karnofsky-performance-status score of at least 60 or equivalent (see Rationale).

NCCN 1, 2A, and 2B recommendations in accordance with Coverage Policy #2000030.

Dosing

The prescribed regimen must be in compliance with FDA-approved dosing, with a dosing regimen of 7.4 GBq (200 mCi) every 8 weeks for a total of 4 doses (limited to one 4-dose regimen per lifetime).

Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.

Somatostatin Analogs

Before initiating Lutathera®: Discontinue long-acting somatostatin analogs (e.g., long-acting octreotide) for at least 4 weeks prior to initiating Lutathera®. Administer short-acting octreotide as needed; discontinue at least 24 hours prior to initiating Lutathera®.

During Lutathera® treatment: Administer long-acting octreotide 30 mg intramuscularly between 4 to 24 hours after each Lutathera® dose. Do not administer long-acting octreotide within 4 weeks of each subsequent Lutathera® dose. Short-acting octreotide may be given for symptomatic management during Lutathera® treatment, but must be withheld for at least 24 hours before each Lutathera® dose.
Following Lutathera® treatment: Continue long-acting octreotide 30 mg intramuscularly every 4 weeks after completing Lutathera® until disease progression or for up to 18 months following treatment initiation.

Amino Acid Solution

Administer IV amino acid solution in accordance with FDA labeling when infusing Lutathera®.

Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria

Lutathera® does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.

For members with contracts without primary coverage criteria, Lutathera® is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.

For any other indication than those listed above as meeting primary coverage criteria.
For any doses that exceed the FDA labeling of 4 dose
For patients previously treated with Yttrium-90 or planned comitant treatment with Yttrium-90.

Effective May 2018 - March 2019

Effective May 01, 2018, Prior Approval is required for Lutetium Lu 177 Dotate (Lutathera®)

Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria

Lutetium Lu 177 dotatate meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness and is covered for the following indications:

Treatment of well-differentiated somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults when all of the following conditions are met:

Tumors must be metastasized or locally advanced, inoperable, and showed disease progression during treatment with a somatostatin analogue (octreotide or lanreotide) AND
Patients must have a Karnofsky-performance-status score of at least 60 or equivalent (see Rationale).

Dosing:

The prescribed regimen must be in compliance with FDA-approved dosing, with a dosing regimen of 7.4 GBq (200 mCi) every 8 weeks for a total of 4 doses (limited to one 4-dose regimen per lifetime).

Somatostatin Analogs

Before initiating Lutathera®: Discontinue long-acting somatostatin analogs (e.g., long-acting octreotide) for at least 4 weeks prior to initiating Lutathera®. Administer short-acting octreotide as needed; discontinue at least 24 hours prior to initiating Lutathera®.

During Lutathera® treatment: Administer long-acting octreotide 30 mg intramuscularly between 4 to 24 hours after each Lutathera® dose. Do not administer long-acting octreotide within 4 weeks of each subsequent Lutathera® dose. Short-acting octreotide may be given for symptomatic management during Lutathera® treatment, but must be withheld for at least 24 hours before each Lutathera® dose.

Following Lutathera® treatment: Continue long-acting octreotide 30 mg intramuscularly every 4 weeks after completing Lutathera® until disease progression or for up to 18 months following treatment initiation.

Amino Acid Solution

Administer IV amino acid solution in accordance with FDA labeling when infusing Lutathera®.

Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria

Lutathera® does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.

For any other indication than those listed above as meeting primary coverage criteria.
For any doses that exceed the FDA labeling of 4 dose
For patients previously treated with Yttrium-90 or planned comitant treatment with Yttrium-90.

Effective Prior to May 2018

Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria

Lutetium Lu 177 dotatate meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness and is covered for the following indications:

Treatment of well-differentiated somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults when all of the following conditions are met:

Tumors must be metastasized or locally advanced, inoperable, and showed disease progression during treatment with a somatostatin analogue (octreotide or lanreotide) AND
Patients must have a Karnofsky-performance-status score of at least 60 or equivalent (see Rationale).

Dosing:

The prescribed regimen must be in compliance with FDA-approved dosing, with a dosing regimen of 7.4 GBq (200 mCi) every 8 weeks for a total of 4 doses (limited to one 4-dose regimen per lifetime).

Somatostatin Analogs

Before initiating Lutathera®: Discontinue long-acting somatostatin analogs (e.g., long-acting octreotide) for at least 4 weeks prior to initiating Lutathera®. Administer short-acting octreotide as needed; discontinue at least 24 hours prior to initiating Lutathera®.

During Lutathera® treatment: Administer long-acting octreotide 30 mg intramuscularly between 4 to 24 hours after each Lutathera® dose. Do not administer long-acting octreotide within 4 weeks of each subsequent Lutathera® dose. Short-acting octreotide may be given for symptomatic management during Lutathera® treatment, but must be withheld for at least 24 hours before each Lutathera® dose.

Following Lutathera® treatment: Continue long-acting octreotide 30 mg intramuscularly every 4 weeks after completing Lutathera® until disease progression or for up to 18 months following treatment initiation.

Amino Acid Solution

Administer IV amino acid solution containing L-lysine and L-arginine 30 minutes before each dose of Lutathera®.

Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria

Lutathera® does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.

For any other indication than those listed above as meeting primary coverage criteria.
For any doses that exceed the FDA labeling of 4 dose
For patients previously treated with Yttrium-90 or planned comitant treatment with Yttrium-90.

Rationale:

The safety and efficacy of Lutathera® for somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs) has been evaluated in one international multicenter open-label phase 3 trial.

Eligible patients were adults who had midgut neuroendocrine tumors that had metastasized or were locally advanced, that were inoperable, that were histologically confirmed and centrally verified, and that showed disease progression on either CT or MRI over the course of a maximum period of 3 years during treatment with octreotide LAR (20 to 30 mg every 3 to 4 weeks for at least 12 weeks before randomization). Patients were required to have a Karnofsky performance-status score of at least 60, have somatostatin receptors present on all target lesions, and have well differentiated histologic features. Well differentiated histologic features defined as a Ki67 index (% of cells that are positive for Ki67 as determined by immunostaining of the primary tumor) of 20% or less.

Patients were randomly assigned 1:1 to receive Lutathera® plus best supportive care (n=116), consisting of octreotide long-acting 30 mg every 4 weeks, or high-dose long acting octreotide (n=113), 60 mg every 4 weeks. Median time since diagnosis was 3.8 years in treatment group vs 4.8 years in control group. Ileum (73%) was the primary tumor site.

Median progression-free survival not met in treatment group and was 8.4 months in control. (95% CI, 5.8 to 9.1). Data not yet mature to provide median overall survival. At pre-specified analysis 14 deaths in treatment group vs 26 deaths in control group. Estimated risk of death was 60% lower in treatment group. (HR for death (0.40; P = 0.004).

Karnofsky Performance Scale

The Karnofsky Performance Status Scale classifies patients based on their functional impairment. The scale ranges from 0 (death) to 100 (normal, no evidence of disease).

The Karnofsky Performance Scale (Karnofsky, 1948)

100 Normal; no evidence of disease

90 Able to carry on normal activity; minor signs or symptoms of disease.

80 Normal activity with effort; some signs or symptoms of disease.

70 Cares for self; unable to carry on normal activity or to do active work

60 Requires occasional assistance, but is able to care for most of their personal needs

50 Requires considerable assistance and frequent medical care.

40 Disabled; requires special care and assistance.

30 Severely disabled; hospital admission is indicated although death not imminent.

20 Very sick; hospital admission necessary; active supportive treatment necessary.

10 Moribund; fatal processes progressing rapidly.

0 Death

2019 Update

A literature search conducted through March 2019 did not reveal any new information that would prompt a change in the coverage statement.

2020 Update

Annual policy review completed with a literature search using the MEDLINE database through April 2020. No new literature was identified that would prompt a change in the coverage statement.

2021 Update

Annual policy review completed with a literature search using the MEDLINE database through April 2021. No new literature was identified that would prompt a change in the coverage statement.

July 2021 Update

In the phase 3 NETTER-1 trial, patients with advanced, progressive midgut neuroendocrine tumours (NET) were randomized to 177Lu-Dotatate (every 8 weeks, four cycles) plus octreotide long-acting release (LAR) or to octreotide LAR 60 mg. Primary endpoint was progression-free survival (PFS). Analyses of PFS by baseline factors, including liver tumor burden, ALP elevation, and target lesion size, were performed using Kaplan-Meier estimates; hazard ratios (HRs) with corresponding 95% CIs were estimated using Cox regression.

Significantly prolonged median PFS occurred with 177Lu-Dotatate versus octreotide LAR 60 mg in patients with low (< 25%), moderate (25-50%), and high (> 50%) liver tumor burden (HR 0.187, 0.216, 0.145), and normal or elevated ALP (HR 0.153, 0.177), and in the presence or absence of a large target lesion (diameter > 30 mm; HR, 0.213, 0.063). Within the 177Lu-Dotatate arm, no significant difference in PFS was observed amongst patients with low/moderate/high liver tumor burden (P = 0.7225) or with normal/elevated baseline ALP (P = 0.3532), but absence of a large target lesion was associated with improved PFS (P = 0.0222). Grade 3 and 4 liver function abnormalities were rare and did not appear to be associated with high baseline liver tumor burden.

Lu-Dotatate demonstrated significant prolongation in PFS versus high-dose octreotide LAR in patients with advanced, progressive midgut NET, regardless of baseline liver tumor burden, elevated ALP, or the presence of a large target lesion. (Strosberg J, Kunz PL, Hendifar A, 2020)

In the Phase II (ERASMUS) trial, patients (N = 1214) with neuroendocrine tumors and positive 111In-DTPA-octreotide scintigraphy were treated with Lutetium Lu 177 dotatate. For safety analysis, 610 patients treated with a cumulative dose of at least 100 mCi (3.7 GBq) Lu-DOTATATE were included. A subgroup of 443 Dutch patients who were treated with a cumulative dose of at least 600 mCi (22.2 GBq) Lu-DOTATATE before 2013 was further analyzed for efficacy and survival.

The objective response rate of the total group of patients was 39%. Stable disease was reached in 43% of patients. Progression-free survival (PFS) and overall survival (OS) for all NET patients were 29 months [95% confidence interval (CI), 26-33 months] and 63 months (95% CI, 55-72 months). Long-term toxicity included acute leukemia in four patients (0.7%) and myelodysplastic syndrome in nine patients (1.5%). No therapy-related long-term renal or hepatic failure occurred.

PRRT with Lu-DOTATATE is a favorable therapeutic option in patients with metastatic bronchial and gastroenteropancreatic NETs that express somatostatin receptors. PRRT with Lu-DOTATATE is safe with few side-effects and shows good response rates with PFS of 29 months and OS of 63 months. (Brabander T, van der Zwan WA, Teunissen JJM, 2017)

2022 Update

Annual policy review completed with a literature search using the MEDLINE database through July 2022. No new literature was identified that would prompt a change in the coverage statement.

2023 Update

Annual policy review completed with a literature search using the MEDLINE database through July 2023. No new literature was identified that would prompt a change in the coverage statement.

CPT/HCPCS:

References:

Karnofsky DA, Abelmann WH, Craver LF, Burchenal JH.(1948) The Use of the Nitrogen Mustards in the Palliative Treatment of Carcinoma – with Particular Reference to Bronchogenic Carcinoma. Cancer. 1948;1(4):634-56.

Brabander T, van der Zwan WA, Teunissen JJM, et. al.(2017) Long-Term Efficacy, Survival, and Safety of [177Lu-DOTA0,Tyr3]octreotate in Patients with Gastroenteropancreatic and Bronchial Neuroendocrine Tumors. Clin Cancer Res. 2017 Aug 15;23(16):4617-4624. doi: 10.1158/1078-0432.CCR-16-2743. Epub 2017 Apr 20. PMID: 28428192.

Colleretto Giacoso (TO) Italy.(2018) Lutathera®® [package insert]. Advanced Accelerator Applications, S.r.l.; 2018

National Comprehensive Cancer Network (NCCN).(2021) NCCN Clinical Practice Guidelines in Oncology™. Neuroendocrine and Adrenal Tumors V3.2021. Revised August 13, 2021. National Comprehensive Cancer Network, Inc. NCCN website: https://www.nccn.org/professionals/physician_gls/pdf/neuroendocrine.pdfAccessed on September 01, 2021.

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